Preparation Of Co-Assembled Paclitaxel/Chitosan Nanofibers And Their Application In Drug-Eluting Stents

Cardiovascular disease has become one of the greatest killers of the public health,and stenting treatment for cardiovascular disease has been shown to have prominent curative effect,so the study of stents has important significance.Drug-eluting stent(DES),based on the bare-metal stents,whose surface coating can release drugs to prevent restenosis.Since DES has remarkable curative effect,it has attracted much attention.The current main problems of DES study are complex preparation method,low drug loading content and unsatisfactory carrier biocompatibility,therefore,the purpose of our study is to develop coating materials which are easy to be prepared,and also have high drug loading and good carrier biocompatibility for DES.In this study,drug-loading nanofibers(NFs)were prepared through intermolecular co-assembly using paclitaxel(PTX)and chitosan(CS)as raw materials.The characterization results demonstrated PTX and CS can co-assembled into NFs under certain conditions,the prepared PTX/CS NFs are nanometer level(20-400nm)in diameter and millimeter level in length.The PTX/CS NFs are core-shell structures,and PTX may co-assemble with CS through non-covalent interactions,such as ?-? stacking,hydrogen bonds,hydrophobic interaction and Van der Waals forces.Furthermore,experiments demonstrated the PTX/CS NFs have high drug loading content(>40 wt.%),well controlled drug release,low cytotoxicity(NIH/3T3)and good hemocompatibility.In addition,the hydrophilic and flexible properties of PTX/CS NFs make them can be easily coated on stent to prepare DES.The PTX/CS NFs coating has enough strength and toughness for DES,slow drug release and can significantly inhibit platelet adhesion.On the basis of the original PTX/CS NFs,we further modified the surface of PTX/CS NFs with hydrophilic phosphoryl choline groups to improve the blood compatibility and decrease the protein and blood platelet adhesion,which can effectively reduce the formation of blood clots.At the same time,we used the layer by layer(LBL)method for optimal performance.Therefore,the random copolymer poly(2-methacryloyloxyethyl phosphorylcholine-co-methacrylic acid)(PMA)was synthesized by free radical polymerization method,then PMA modified PTX/CS NFs coating was obtained by electrostatic interaction between CS and PMA.Experimental results proved the cell outer membrane mimetic PTX/CS-PMA NFs surfaces have lower cytotoxicity,better blood compatibility,lower protein adsorption and platelet adhesion compared with PTX/CS NFs coating,which proved PTX/CS-PMA NFs' application potential for drug eluting stents.